PROLONGED ALLOGRAFT SURVIVAL IN CYNOMOLGUS MONKEYS TREATED WITH A MONOCLONAL-ANTIBODY TO THE HUMAN TYPE-I INTERFERON RECEPTOR AND LOW-DOSESOF CYCLOSPORINE

A monoclonal antibody (mAb) directed against the extracellular domain of the IFNAR1 chain of the human interferon-alpha (IFN-alpha) receptor (IFN-alpha R), which inhibits activation of the Jak-Stat signal trans duction pathway, administered together with a subeffective dose of cyc losporine induced prolonged survival of skin allografts in major histo compatibility complex (MHC) divergent cynomolgus monkeys, Skin biopsie s from animals treated with anti-IFN-alpha R mAb and cyclosporine reve aled very low levels of MHC class I and class II antigen expression an d the absence of histologic signs of rejection. Monkey antibodies (IgG ) to the mouse antihuman IFN-alpha R mAb were not detected in the seru m of any of the animals treated with the anti-IFN-alpha R mAb either a lone or together with cyclosporine, The anti-IFN-alpha R mAb abrogated activation of the Jak-Stat signal transduction pathway in IFN-treated cells. These results, which show that selective and long-lasting immu nosuppression can be obtained by short-term administration of an IFN-a lpha antagonist together with a subeffective dose of cyclosporine, may have important implications for the therapy of human allograft reject ion.